Description: The Immunology Program consists of 12 members with research interests in basic and clinical immunology, including a strong emphasis on the application of basic immunologic findings to the treatment of hematopoietic malignancies and solid tumors. Several laboratories pursue fundamental studies in murine lymphocyte biology and genetics. Dr. Ulrich Hammerling has contributed to murine immunogenetics and the characterization of human cell surface antigens, and has recently been focusing on the role of vitamin A in lymphocyte metabolism and immunodeficiency. Dr. Janko Nikolic-Zugic studies the developmental biology of murine thymocytes, with a particular emphasis on the role of T-cell receptor alpha rearrangements in thymic selection and apoptosis. Dr. Howard Petrie (recruited as a new assistant member in the Immunology Program in 1993) investigates the membrane events and signaling pathways that influence differentiation, cell division, and programmed cell death in murine thymocyte development. Dr. Osias Stutman continues to study cell-mediated immune responses and the immunologic function of tumor necrosis factor. Several investigators have interests in the immunogenetics of the human major histocompatibility complex (MHC). Dr. Janet Lee is studying an immunodeficiency disease designated the Bare Lymphocyte Syndrome, as a model for understanding transcriptional regulation of MHC class II molecules. Dr. Soo Young Yang is investigating the alloreactivity responsible for graft failure or graft-versus-host disease, and is also identifying DNA binding proteins that regulate class I transcription, and evaluating fine genetic polymorphisms in MHC class I and class II genes. Dr. Bo Dupont has made many contributions to the immunogenetics of the human MHC. He also has a current effort dedicated to understanding the regulation and function of CD28/B7 costimulation in T-cell responses. Several Immunology Program members work at an interface between translational research and clinical application, and employ immunologic strategies to treat hematopoietic malignancies by bone marrow transplantation (BMT), and to treat solid tumors with monoclonal antibodies and cytokines. Dr. Richard O'Reilly studies the immunobiology of bone marrow transplantation, and directs the pediatric BMT unit that treats leukemia and congenital immunodeficiencies. A second new addition to the Immunology Program (a joint recruitment with Cancer Prevention and Control), Dr. Michel Sadelain, brings expertise in the construction and use of retroviral vectors for gene therapy. Cancer Immunology is an area of considerable emphasis and tradition. Dr. Lloyd Old continues to study cell surface antigens on murine and human tumors, with the intent of developing immunologic approaches to treating human cancer. Dr. Alan Houghton, Program Head, has a major emphasis on identifying peptide sequences that stimulate the host immune response to tumors (particularly melanoma), and the development of human cancer vaccines. Dr. Kenneth Lloyd conducts fundamental biochemical analysis of glycoproteins and glycolipids, with a particular emphasis on defining the immunogenicity of gangliosides and blood group antigens on human solid tumors. Ten of the twelve Immunology Program members have NIH support, and the group has a total of nine R01s and two R29s. Furthermore, Drs. O'Reilly and Houghton are principal investigators on NCI program projects. The program makes extensive use of Center shared resources.